Reticuloendotheliosis virus (REV) is an avian oncornavirus. Unlike other C-type viruses, it is highly virulent: its incubation period may be as short as five days, and mortality approaches 100%. It is the prototype of a recently proposed group which now includes three other viruses. The objectives of this research proposal are four-fold. REV does not transform chick embryo fibroblast cultures (CEF), and the virus produced by them is attenuated. We have recently isolated transformed bone marrow lines which produce infectious REV. We would like to define the basis for the attenuation of CEF-REV. Three possible explanations are that CEF cultures select against an essential helper, that envelope glycoproteins are altered, or that CEF-REV contains and inadequate level of DNA polymerase. The second objective involves the investigation of the replication of REV in vitro. We plan to focus our attention on the synthesis and cellular location of virus-directed proteins, employing combined immunological and cell fractionation techniques. The role of the mitochondria in REV replication will be investigated. We will determine he infectivity of isolated mitochondria and their extracted DNA's and the effect of specific inhibitors of protein synthesis. We will investigate the possibility that viral proteins or virions are synthesized in isolated mitochondria. The third objective is to determine the relationship between REV and the other viruses in the group, which have been isolated from two other avian species. Since a 'group' should have a common group- specific antigen, we will prepare antiserum to the major internal protein of REV. This will be of value in confirming the membership of the group and identifying new members. The fourth objective is to investigate the involvement of various cell types and the interactions of the immune system in this rapidly lethal neoplastic disease.